Srivastava, Simran and Kumar, Sahil and Mishra, Suman and Rajmani, Raju S and Singh, Randhir and Dutta, Somnath and Ringe, Rajesh Prakash and Varadarajan, Raghavan (2026) Development of a thermostable and broadly neutralizing pan-sarbecovirus vaccine candidate. ACS Infect. Dis., 12 (1). pp. 104-118.
Full text not available from this repository. (Request a copy)Abstract
Zoonotic spillover of sarbecoviruses to humans resulted in the SARS-CoV-1 outbreak in 2003 and the current COVID-19 pandemic caused by SARS-CoV-2. In both cases, the viral spike protein (S) is the principal target of neutralizing antibodies that prevent infection. Within the spike, the immunodominant receptor-binding domain (RBD) is the primary target of neutralizing antibodies in COVID-19 convalescent sera and vaccine recipients. We have constructed stabilized RBD derivatives of different sarbecoviruses: SARS-CoV-1 (Clade 1a), WIV-1 (Clade 1a), RaTG13 (Clade 1b), RmYN02 (Clade 2), and BtKY72 (Clade 3). Stabilization enhanced yield by 3-23-fold. The RBD derivatives were conformationally intact, as assayed by binding to multiple broadly neutralizing antibodies. The stabilized RBDs show significant enhancement in apparent Tm, exhibit resistance to a 2-h incubation at temperatures up to 60 °C in PBS in contrast to the corresponding WT RBDs, and show prolonged stability of over 15 days at 37 °C after lyophilization. In mice immunizations, both stabilization and trimerization significantly enhanced elicited neutralization titers by �100-fold. The stabilized RBD cocktail elicited highly neutralizing titers against both homologous and heterologous pseudoviruses. The immunogenicity of the vaccine formulation was assessed in both na\"\ive and SARS-CoV-2 preimmunized mice, revealing an absence of immune imprinting, thus indicating its suitability for use in future sarbecovirus-origin epidemics or pandemics.
| Item Type: | Article |
|---|---|
| Additional Information: | Copyright of this article belongs to ACS. |
| Uncontrolled Keywords: | SARS-CoV-2; coronavirus; efficacy; lyophilized; preparedness; protein-subunit; thermostability; yield |
| Subjects: | Q Science > QR Microbiology |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 01 Feb 2026 03:27 |
| Last Modified: | 01 Feb 2026 03:27 |
| URI: | http://crdd.osdd.net/open/id/eprint/3207 |
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